title: Polymorphisms in the tumor necrosis factor alpha and interleukin 1-beta promoters with possible gene regulatory functions increase the risk of preterm birth.
abstract: OBJECTIVE
  To investigate the relation between 19 selected single nucleotide polymorphisms in three cytokine genes, tumor necrosis factor alpha (TNFA), interleukin 1-beta (IL1B) and interleukin 6 (IL6) and preterm birth (<37 weeks' gestation).
  
  
  METHODS
  Case-control association study.
  
  
  METHODS
  A total of 117 singleton pregnant Danish Caucasian women, including 62 preterm birth cases and 55 controls (birth>or=37 weeks).
  
  
  METHODS
  Genotyping was performed using TaqMan probes and traditional sequencing. Descriptive statistics were carried out with Fisher's exact test and Wilcoxon rank-sum test. All genetic data were tested for Hardy-Weinberg equilibrium and analyzed using logistic regression, 2x2 proportions or chi(2). Haplotypes were estimated for each gene and permutation used for association testing.
  
  
  RESULTS
  Women carrying the TNFA -857 C>T rare allele (T) and those homozygous for the IL1B -31 T>C and IL1B -511 C>T rare alleles (C and T) have an increased risk of preterm birth with OR 3.1 (95% CI: 1.0-10.3) and OR 6.4 (95% CI: 1.3-60.5), respectively. Two estimated TNFA haplotypes were associated with preterm birth with OR 3.1 (p=0.037) and OR 2.7 (p=0.045).
  
  
  CONCLUSIONS
  Polymorphisms in the cytokine genes TNFA and IL1B may increase the risk of preterm birth, possibly by a dysregulation of the immune system in pregnancy.
authors.affiliation: Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark. mvh@ssi.dk
authors.forename: Mads Vilhelm
authors.initials: MV
authors.lastname: Hollegaard
authors.forename: Jakob
authors.initials: J
authors.lastname: Grove
authors.forename: Poul
authors.initials: P
authors.lastname: Thorsen
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Susanne
authors.initials: S
authors.lastname: Mandrup
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.forename: Bent
authors.initials: B
authors.lastname: Norgaard-Pedersen
authors.forename: Karen R
authors.initials: KR
authors.lastname: Wojdemann
authors.forename: Ann
authors.initials: A
authors.lastname: Tabor
authors.forename: Jorn
authors.initials: J
authors.lastname: Attermann
authors.forename: David Michael
authors.initials: DM
authors.lastname: Hougaard
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha